CA02脂质体注射液大鼠长期毒性试验

目的：观察大鼠连续腹腔注射CA02脂质体产生的毒性反应与靶器官损害的可逆性.方法：设高、中、低剂量组和溶剂对照组,分别腹腔注射给予CA02脂质体注射液45.0,22.5,11.25 mg·kg^-1和等容量生理盐水（NS）对照品,通过对大鼠血液学、血液生物化学和病理靶向相关指标的观察,考察CA02脂质体对大鼠的毒性反应及程度.结果：连续腹腔注射CA02脂质体13周,动物全部存活,高剂量组大鼠PLT降低（P＜0.01）、CREA降低（P＜0.05）、TCHO升高（P＜0.01）较溶剂对照组比较的差异有统计学意义,但停药4周后能恢复正常.中、小剂量组未见明显毒性反应.停药后各剂量组均未见迟缓性毒性发生.结论：大剂量[45.0 mg·（kg·d）^-1]（相当于临床人用量的450.0倍）CA02腹腔注射对肾功能有一定的损害性,但为可逆性.

Long-Term Toxic of Liposomes CA02 Injection in Rats

Objective： To investigate the toxicity and the impaired reversibility on target organ after injecting liposomes CA02 in rats. Method： The high, medium and low dose group and solvent control group were seted, CA02 were given intraperitoneal injection of liposome injection 45.0,22. 5,11.25 mg·kg^- 1, and equal volume of normal saline （NS） reference substance. The rat＇ s hematology, blood biochemistry and pathology related indicators targeted were observated, the extent of CA02 liposomes toxicity were inspected in rats. Result： After intraperitoneal injection of hposome CA02 13 weeks, all animals survived, the high dose group PLT decreased （P 〈 0. 01 ）, CREA decreased （ P 〈 0.05 ） , TCHO increased （ P 〈 0. 01 ）, and compared with solvent control group the differences were statistically significant, but returned to normal after 4 weeks. No evident toxicity reaction was seen in the medium and low dosage groups. No flaccid toxicity was found in each dosage group after drug withdrawal. Conclusion： Intraperitoneally injecting liposomes CA02 with high dosage [ 45.0 mg· （ kg· d） - 1 ] in rats has a certain reversibility for renal damage.